7 REV 1406 Lecture

CHAPTER 7 LECTURE SLIDES
Prepared by
Brenda Leady
University of Toledo
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Cellular respiration
Process by which living cells obtain energy from organic molecules and release waste products Primary aim to make ATP and NADH Nutrients are broken down and re-arranged into high energy molecules. Metabolism: all the chemical processes of the body (cell)
When we breath we take in the oxygen needed for cellular respiration)
Cellular respiration
Anaerobic respiration
Without
oxygen consumption.
Aerobic respiration uses oxygen

O2
consumed and CO2 released
Focus on glucose but other organic molecules also used.
Glucose metabolism
C6H12O6 + 6O2 6CO2 + 6H2O ATP, NADH, FADH2 4 metabolic pathways Glycolysis Breakdown of pyruvate to an acetyl group Citric acid cycle Oxidative phosphorylation
4
1. 2.
3.
4.
Glycolysis: Glucose C C C C C C
Outer mitochondrial membrane

Cytosol
2 pyruvate 2 C C C 2 NADH 2 NADH 2 pyruvate
Mitochondrial matrix
Inner mitochondrial membrane
Breakdown of pyruvate: 2 pyruvate 2 C C C
6 NADH 2 FADH2
Citric acid cycle: 2 acetyl

2 C C
4 Oxidative
phosphorylation: The oxidation of NADH and FADH2 via the electron transport chain provides energy to make more ATP via the ATP synthase. O2 is consumed.
2CO2 + 2acetyl 2 C C
2 CO2 2 acetyl 4 CO2 2 CO2
2 CO2
+2 ATP
+2 ATP
+3034 ATP
Via substrate-level phosphorylation
Via substrate-level phosphorylation
Via chemiosmosis 5
Stage 1: Glycolysis
Glycolysis can occur with or without oxygen. Steps in glycolysis nearly identical in all living species 10 steps in 3 phases
Energy investment (2 ATP) 2. Cleavage 3. Energy liberation
1.
6
3 phases of glycolysis
1.
Energy investment

Steps 1-3 2 ATP hydrolyzed to create fructose-1,6 bisphosphate Steps 4-5 6 carbon molecule broken into two 3 carbon molecules of glyceraldehyde-3-phosphate Steps 6-10 Two glyceraldehyde-3-phosphate molecules broken down into two pyruvate molecules producing 2 NADH and 4 ATP
7
2.
Cleavage

3.
Energy liberation

Net yield in ATP of 2
Glycolysis
occurs in the cytosol
C C C C C C
CH2OH H H OH HO H
O H
H OH OH
9
Glucose
Phase 1 Energy investment phase

2 ATP are hydrolyzed and the P- from the ATP is attached to the glucose
C C C C C C
CH2OH H H OH HO H O H H OH OH ATP ATP
C C C C C C
Step 1 Step 2 Step 3
P OCH2 H H OH O HO H CH2O P OH
Glucose
Fructose-1,6bisphosphate
10
This phase raises the free energy level of the glucose which allows later Rxns to be exergonic.
The cleavage phase (steps 4-5) breaks the six carbon

molecule into 2 three carbon molecules (glyceraldehyde-3-phsphate) Cleavage phase C C C
H
Energy investment phase

C C C C C C
CH2OH H H OH HO O H H OH ATP ATP OH H Step 1 Step 2 Step 3 P OCH2 H H O HO CH2O P OH
Step 4
Step 5
CHOH CH2O P
C C C C C C
C C C
H C O
OH
Glucose
CHOH CH2O P
Two molecules of glyceraldehyde3-phosphate

11
Step 6, glyceraldehyde-3-phosphate is oxidized to yield NADH. (x2)

Steps 7 and 10, 4 ATP are made by substrate level phosphorolation.
Energy investment phase
Cleavage phase
C C C
H Step 4 Step 5 C O
Energy liberation phase Steps 6-10 Liberates energy to produce energy intermediates
Step 6 Step 7 Step 8 Step 9
C C C
O O O
Step 10 C C
CHOH
C C C C C C
CH2OH H H OH HO H O H H OH OH ATP ATP Step 1 Step 2 Step 3 P
C C C C C C
OCH2 H H OH O HO H CH2O P OH
CH2O P Pi NADH ATP ATP
CH3
C C C
H C O
C C C
O C C Pi NADH ATP ATP O O
Glucose
CHOH CH2O P
CH3
Two molecules of glyceraldehyde3-phosphate
Two molecules of pyruvate
Glycolysis Net yield is 2 ATP and 2 NADH and 2 pyruvate molecules.

12
Glycolysis
CH2OH
H O H
ATP
H OH HO
H
H OH
OH
13
Glucose
1. Glucose is phosphorylated by ATP.
CH2OH
ATP ADP
OCH2 H H OH
O H H OH H OH
H H OH HO H
O
H
OH OH
Hexokinase
HO
Glucose
Glucose-6-phosphate
14
2. Glucose-6-phosphate is rearranged into fructose-6-phosphate
CH2OH H H OH HO H OH O H H
ATP
ADP
P OCH2 H O H
P OCH2 O H
Phosphogluco isomerase
ATP
CH2OH HO OH
H OH
OH
Hexokinase
H OH
HO H OH
OH
Glucose
Glucose-6-phosphate
Fructose-6-phosphate
15
3. Fructose-6-phosphate is phosphorylated to make fructose-1,6-bisphosphate (ATP is used)
CH2OH H H OH HO H O H H
ATP
ADP
P OCH2 H H OH HO H O H H OH OH
P OCH2 O H H HO H
ATP
ADP
CH2OH OH
P OCH2 H OH
O HO H
CH2O P
OH OH
H
Phosphofructo kinase
OH
Aldolase
Hexokinase
Phosphogluco isomerase OH
Glucose
Glucose-6-phosphate Fructose-6-phosphate
Fructose-1,6-bisphosphate
16
4. Fructose-1,6-bisphosphate is cleaved into Dihydroxyacetone and Glyceraldehyde-3-phosphate

P OCH 2 C O
CH2OH
Dihydroxyacetone phosphate
Isomerase
CH2OH H H OH HO H O H H
ATP
ADP P OCH2
P OCH2 O H O H H HO H
ATP
ADP
H P OCH2 H OH O HO H CH2O P C O
CH2OH OH
H OH
OH
Hexokinase
H OH OH
CHOH OH
Aldolase
HO H
H
OH
CH2O P
Glucose
Glucose-6-phosphate
Glyceraldehyde-3phosphate (X2)
Dihydroxyacetone is isomerized into another glyceraldehyde-3-phosphate the result is 2 glyceraldehyde-3-phosphate

17
5. The Dihydroxyacetone phosphate is Isomerized into Glyceraldehyde-3-phosphate.
OCH2
O C CH2OH
Isomerase
H C O
CHOH CH2O P
Glyceraldehyde-3phosphate
(X2)
18
Glycolysis: Glucose
2 NADH
2 NADH 6 NADH 2 FADH2
P OCH 2
2 pyruvate
Breakdown of pyruvate
2 CO2
Citric acid cycle 2 CO2 2 CO2
CH2OH
Oxidative phosphorylation
Isomerase
+2 ATP
CH2OH H H OH HO H O H H OH OH
Hexokinase ATP ADP P OCH2
+2 ATP
+3034 ATP ATP ADP
P OCH2 O H O H H HO H
H P OCH2 H OH O HO H CH2O P C O
H H OH
CH2OH OH
CHOH OH
Aldolase
HO
H
OH
OH
H
CH2O P
Glucose
Glucose-6-phosphate
Glyceraldehyde-3phosphate ( 2)
19
6. Glyceraldehyde-3-phosphate is oxidized to 1,3bisphosphoglycerate with the production
of NADH
OCH2 C CH2OH
Isomerase
The phosphate group is destabilized making it ready for exergonic reaction

Unstable phosphate bond
2 NADH
H C CHOH CH2O P O
2 NAD+
+2 H+ P
~ OC
CHOH
Glyceraldehyde3-phosphate dehydrogenase
CH2O 2 Pi
1, 3 -bisphosphoglycerate (2)
20
7. A phosphate is removed from 1,3-bisphosphoglycerate to produce 3-phosphoglycerate. The phosphate is transferred to ADP to make ATP. (x2, yield 2 ATP)
P OCH2 C O
CH2OH
Isomerase

2 NADH H C O 2 NAD+ +2 H+ P 2 ADP 2 ATP O C O
~ OC
CHOH CH2O P Glyceraldehyde3-phosphate 2 Pi dehydrogenase
CHOH CH2O P Phosphoglycero kinase
CHOH CH2O P
3-phosphoglycerate (2)
21
8. The phosphate group is moved in 3-phosphoglycerate to form 2-phosphoglycerate
OCH2 C O
CH2OH
Isomerase

2 NAD+ O
H C
2 NADH +2 H+
P
2 ADP
2 ATP
O C O
O C O P
~ OC
CHOH CH2O
CHOH P
Phosphoglycero kinase CH2O P Phosphoglycer o mutase
HCO
CH 2OH
22
9. A water molecule is removed from 2phosphoglycerate to form Phosphoenolpyruvate. The phosphate group is destabilized in the process.
OCH2 C O
CH2OH
Isomerase

2 NAD+ O 2 NADH +2 H+ P 2 ADP 2 ATP O C O O C HCO P Phosphoglycer o mutase O P Enolase 2 H2O

O C CO CH2 O
H C
~ OC
CHOH CH2O P
CHOH Phosphoglycero CH2O kinase
~P
CH 2OH
Phosphoenolpyruvate (2)
23
10. A phosphate is removed from Phosphoenolpyruvate to form Pyruvate. The phosphate is transferred to ADP.
OCH2 C O
CH2OH
Isomerase
2 H2O
2 NAD+ 2 NADH +2 H+ P 2 ADP 2 ATP O C O O C HCO P Phosphoglycer o mutase O P Enolase 2 H2O

O C O 2 ADP 2 ATP O C C Pyruvate kinase CH3 O O
H C O
~ OC
CHOH CH2O P
CHOH Phosphoglycero CH2O kinase
CO ~ P CH2
CH 2OH
Phosphoenolpyruvate (2)
Pyruvate (2)
The end products of glycolysis is 2 pyruvate, 2 H+, 2 NADH, 2 ATP and 2 H2O
24
Control of glycolyis
Feedback inhibition occurs when ATP concentrations in the cell are high. ATP binds to the allosteric site in fructokinase preventing the action of this enzyme (step 3). This prevents the further breakdown of glucose inhibiting the overproduction of ATP.
Stage 2:
Breakdown of pyruvate to an acetyl group
In eukaryotes, pyruvate is transported to the mitochondrial matrix Broken down by pyruvate dehydrogenase Molecule of CO2 removed from each pyruvate Remaining acetyl group attached to CoA to make acetyl CoA 1 NADH is made for each pyruvate
26
O C O C O Outer CH3 membrane channel H+/pyruvate symporter H+ O C O
C O CH3
+ CoA SH
NAD+
Pyruvate dehydrogenase S CoA C O + CO2 + NADH CH3 Acetyl CoA
Pyruvate travels through a channel in the outer membrane and through an H+/pyruvate Symporter in the inner membrane to reach the matrix
27
O C O C O Outer CH3 membrane channel H+/pyruvate symporter H+ O C O
C O CH3
+ CoA SH
NAD+
Pyruvate dehydrogenase S CoA C O + CO2 + NADH CH3 Acetyl CoA
Pyruvate is oxidized to an acetyl group (CO2 and NADH is made). The acetyl group is transferred to a coenzyme-A Acetyl CoA
28
Stage 3: Citric acid cycle

(Acetyl CoA) Metabolic cycle
Particular
molecules enter while others leave, involving a series of organic molecules regenerated with each cycle
Acetyl is removed from Acetyl CoA and attached to oxaloacetate to form citrate or citric acid Series of steps releases 2CO2, 1ATP, 3NADH, and 1 FADH2 Oxaloacetate is regenerated to start the cycle again
29
Glycolysis: Glucose
2 NADH 2 NADH 6 NADH 2 FADH2
2 pyruvate 2 CO2 Breakdown of pyruvate +2 ATP
Citric acid cycle

2 CO2 2 CO2 +2 ATP
NADH
CO2 NADH
+3034 ATP
Citrate C C C C C C 2 C C C C C C 3
CO2 C C C C C 4
1 Citric acid cycle O H2C C S CoA Acetyl CoA C C C C Oxaloacetate 8 C C C C NADH C C C C ATP FADH2 7 6 C C C C GTP 5 C C C C
The citric acid cycle is cyclic because it involves a series of organic molecules that are regenerated after the turn of the cycle. 30
COO
CH2 HO C CH
2
COO
COO
Citrate C C C C C C CoASH 2A
S C CH CoA O
H2O
Citrate synthetase
Acetyl CoA C C
1. An acetyl group from acetyl CoA is attached to oxaloacetate to form citrate

31
COO CH2 HC COO
COO
CH2 HO C CH2 COO
HO
CH COO
Isocitrate C C C C C C
COO
S C CH CoA O
2B
Aconitase
H2O Citrate synthetase
Acetyl CoA C C
2. Citrate is rearranged to an isomer called isocitrate
32
COO CH2 HC COO CH2 HO C CH2 COO COO HO CH COO COO
COO CH2 CH2
+
O
CO2
NADH NAD+ 3
COO
-Ketoglutarate C C C C C
S C CH CoA O
2B Aconitase
Isocitrate dehydrogenase
H2O Citrate synthetase
Acetyl CoA C C
3. Isocitrate is oxidized to a-ketogluterate. (CO2 is released and NADH is formed)
1
33
COO CH2
COO CH2 CH2 C O COO
HC COO
COO CH2 HO C CH2 COO COO HO CH COO
CO2
NADH NAD+ 3
COO
-Ketoglutarate C C C C C 4
CoASH NADH
CH2
CH2 C S O CoA
CO2
NAD+
S
C CH
2B
Aconitase
-Ketoglutarate dehydrogenase
Succinyl-CoA C C C C
CoA
O
H2O
Citrate synthetase
Acetyl CoA C C
4. A-ketogluterate is oxidized as it combines with CoA to form succinyl CoA. (CO2 is released and NADH is formed)
34
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. COO CH2 COO CH2
HC
COO CH2 HO CH
COO
CH2
+
O
CO2
COO
COO COO
NADH NAD+ 3
COO
HO
C
CH2
-Ketoglutarate C C C C C 4 -Ketoglutarate dehydrogenase
CoASH NADH NAD+
CH2 CH2 C S O CoA
CO2
COO
S C CoA O
2B Aconitase
Succinyl-CoA
C C C C 5
GDP + Pi
CH
+ H2O Citrate synthetase CoASH ATP Succinyl-CoA synthetase GTP ADP 1 Succinate C C C C
Acetyl CoA C C
5. Succinyl CoA is broken down to CoA and succinate. This drives the formation of GTP from GDP and P. (GTP can donate a phosphate to ADP to form ATP)
COO CH2 CH2 COO
35
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. COO CH2 HC COO HO CH COO COO COO COO CH2 CH2 C O COO
CO2
CH2
HO C CH2 COO
NADH NAD+ 3
COO
-Ketoglutarate C C C C C 4
CoASH NADH NAD+
CH2 CH2 C S O CoA
CO2
S C CH CoA O
2B Aconitase
-Ketoglutarate dehydrogenase
Succinyl-CoA C C C C
GDP + Pi
+ H2O
Citrate synthetase CoASH ATP Succinyl-CoA synthetase GTP ADP
Acetyl CoA C C
1
Fumarase 7
Succinate dehydrogenase 6 Succinate C C C C

COO
CH2 CH2 COO
FADH2
FAD
6. Succinate is oxidized to fumerate. (FADH2 is made)
Fumarate C C C C
COO CH HC
COO
36
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. COO CH2 HC COO CH2 HO CH COO COO COO COO CH2 CH2 C O
CO2
COO
NADH NAD+ 3
COO
HO
C
CH2
CoASH NADH NAD+
CH2 CH2 C S O CoA
CO2
COO
Citrate C C C C C C
2B Aconitase
CoASH
2A
S C CH CoA O
Succinyl-CoA
C C C C 5
GDP + Pi
+ H2O
Acetyl CoA C C
Citrate synthetase
CoASH
ATP Succinyl-CoA synthetase GTP ADP
1 Fumarase 8 7
Succinate dehydrogenase 6 Succinate C C C C

COO CH2 CH2 COO
7. Fumerate combines with water to form malate.
Malate C C C C
COO HO CH CH2 COO
FADH2 Fumarate C C C C H2O

COO CH HC COO
FAD
37
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. COO CH2 HC COO CH2 HO C CH2 COO COO HO CH COO COO COO CH2 CH2 C O COO
CO2
NADH NAD+ 3
COO
CoASH NADH NAD+
CH2 CH2 C O
+
CoA
CO2
S C CH CoA O
2B Aconitase
Succinyl-CoA C C C C 5
GDP + Pi
+ H2O Citrate synthetase Citric acid cycle Succinyl-CoA synthetase GTP ADP 1 Oxaloacetate C C C C
COO O C CH2 COO
Acetyl CoA C C
ATP CoASH
Malate dehydrogenase 8 NADH NAD+ Malate C C C C

COO CH CH2
Succinate dehydrogenase 6 Fumarase 7 FADH2 Fumarate C C C C FAD Succinate C C C C

COO CH2 CH2
COO
H2O
COO CH HC COO
HO Malate is oxidized to Oxaloacetate. (the cycle can begin again)
COO
38
Control of the citric acid cycle
Competitive inhibition Oxaloacitate is a competitive inhibitor of succinate dehydrogenase (catalizes step 6) When the oxaloacitate level becomes too high, succinate dehydrogenase is inhibited and the citric acid cycle slows down.
On to the oxidative phosphorylation

Up to this point we have yielded 6 molecules of CO2, 4 molecules of ATP, 10 molecules of NADH and 2 molecules of FADH2
Stage 4: Oxidative phosphorylation

High energy electrons are removed from NADH and FADH2 to make ATP Typically requires oxygen Oxidative process involves electron transport chain Phosphorylation occurs by ATP synthase
41
Oxidation: ETC
Electron transport chains (ETC)

Is
a Group of protein and small organic molecules embedded in the inner mitochondrial membrane
These proteins and molecules can accept and donate electrons in a linear manner in a series of redox reactions.
42
Electrons are transferred to components with increasing electronegativity.
The end of the line is Oxygen which is the most electronegative. (final electron acceptor)
Movement of these electrons generates a H+ (proton) electrochemical gradient/ protonmotive force
The
transfer of the electrons is highly exergonic and free energy can be harnessed to pump H+ across the inner mitochondrial membrane creating a proton electrochemical gradient.
The hydrogens (protons) flow through an enzyme (ATP Synthase) down its concentration gradient.
ATP Synthase harnesses free energy from the flow of protons to attach phosphates to ADP generating ATP. Kinetic energy of the H+ gradient is converted to chemical bond energy of ATP This process is called chemiosmosis.
KEY Matrix
Membrane proteins and components accept and Transfer e- in a highly Exergonic Rxn. Which is used to drive H+ against its Concentration gradient.
Intermembrane space
H+ movement e movement
NADH
NADH dehydrogenase I H+ H+ H+
NAD+ + H+ Succinate reductase FADH2 FAD + 2 H- Cytochrome b-c1 III H+ H+ Cytochrome c c H+ H+ II Ubiquinone
H+ H+
Electron transport chain H+
The flow of H+ through the ATP synthase enzyme provides free energy for the phosphorolation of ADP to ATP.
2 H+ + O2 IV H2O
Cytochrome oxidase H+ H+ H+
Matrix ATP synthase H+ ADP + Pi
H+
ATP Inner mitochondrial membrane
H+
ATP synthesis
H+
Intermembrane space
45
Phosphorylation by ATP synthase
Lipid bilayer of inner mitochondrial membrane relatively impermeable to H+

H+ can only pass through ATP synthase
Harnesses the free energy release to synthesize ATP from ADP Chemiosmosis - chemical synthesis of ATP as a result of pushing H + across a membrane
46
NADH oxidation and ATP synthesis

Oxidation of NADH and FADH results in electrochemical gradient used to synthesize ATP (FADH donates H+ to the succinate reductase enzyme) 30-34 ATP molecules per glucose molecule broken down into CO2 and H2O Rarely achieve maximal amount
NADH
used in anabolic pathways H+ gradient used for other purposes

47
ATP synthase
Enzyme Energy conversion- H+ electrochemical gradient or proton motive force converted to chemical bond energy in ATP Racker and Stoeckenius confirmed ATP uses an H+ electrochemical gradient
48
YIELDS
Glycolyis: 2 ATP
Citric Acid Cycle: 2 ATP Oxidative Phosphorylation: 30-34 ATP
ATP synthase
A Rotary machine that makes ATP as it spins
ATP synthase
Vesicle
Bacteriorhodopsin (light-driven H+ pump) ADP Pi
Light rays
No H+ gradient
H+ gradient
ATP
51
H+ passes through the c unit ADP + Pi Causing the Y unit to rotate Clockwise. Each 120 deg. turn Causes a conformational change That attaches P to ADP. Conf. 1: ADP and P bind Conf. 2: ADP and P are bonded Conf 3: ATP is released
ATP
H+ c c
Matrix
c
a Intermembrane space
52
H+
Chemicals can inhibit e- flow along ETC
Cyanide: inhibits cytochrome oxidase

This
shuts down the ETC preventing cells from making enough ATP for survival
Yoshida and Kinosita deomonstrate that the subunit of the ATP synthase spins
Masasuke Yoshida, Kazuhiko Kinosita, and colleagues set out to experimentally visualize the rotary nature of the ATP synthase Released membrane embedded portion and adhered it to a slide Visualize subunit using fluorescence Added ATP to make reaction run backward Rotated counterclockwise to hydrolyze ATP
Rotate
clockwise to synthesize ATP
Experimental level Add purified complex. Conceptual level
3 3 complex
Slide
Add linker proteins and fluorescent actin filaments.
Linker proteins
Fluorescent actin filament
ATP
Control:
ATP
Fluorescence microscope + ATP: counterclockwise rotation
ATP No ATP added ATP added
Rotation No rotation observed. Rotation was observed as shown below. This is a time-lapse view of the rotation in action.
Cancer cells usually favor glycolysis
Many disease associated with alterations in carbohydrate metabolism Warburg effect- cancer cells preferentially use glycolysis while decreasing oxidative phosphorylation Used to diagnose cancers in PET scans Glycolytic enzymes overexpressed in 80% of all types of cancers Caused by genetic and environmental factorsmutations and low oxygen
Other organic molecules
Focus on glucose but other carbohydrates, proteins and fats also used for energy Enter into glycolysis or citric acid cycle at different points Utilizing the same pathways for breakdown increases efficiency Metabolism can also be used to make other molecules (anabolism)
58
Amino Acids and Fats
Can enter the later stages of glycolysis, the citric acid cycle or at different points along the pathway after being modified.

Some breakdown products of proteins enter into the later stages of glycolysis or enter the citric acid cycle. Ex. Acetyl groups from some amino acids can be removed and attached to CoA to become Acetyl CoA which enters the citric acid cycle.

Fats can be broken down to glycerol and 2 fatty acids (acyls). Glycerol can be modified into glyceraldehyde-3-phosphate and enter glycolysis at step 5. The 2 fatty acetyl tails can be removed and combined with CoA Acetyl-CoA then enter the citric acid cycle
After modification proteins and fats use the same enzymes and pathways.
By using the same pathways and enzymes cellular metabolism is more efficient
Proteins
Carbohydrates
Fats
Amino acids
Sugars
Glycerol Fatty acids
Glycolysis: Glucose Glyceraldehyde3-phosphate Pyruvate
Acetyl CoA
Citric acid cycle
63
The McGraw-Hill Companies, Inc./Ernie Friedlander/Cole Group/Getty Images
7.3 Anaerobic metabolism
For environments that lack oxygen or during oxygen deficits

2 strategies
1.
Use substance other than O2 as final electron acceptor in electron transport chain Produce ATP only via substrate-level phosphorylation
64
2.
Other acceptors
KE Y NADH dehydrogenase NADH H+ NAD+ + H+ H+ Ubiquinone Cytochrome b H+ H+ H+ movement e movement
E. coli uses nitrate (NO3-) under anaerobic conditions Makes ATP via chemiosmosis even under anaerobic conditions Nitrate is the final acceptor instead of O2
Cytoplasm
H+ H+ NO3 + 2 H+ Nitrate reductase H+ NO2 + H2O H+
ATP synthase
ADP + Pi
H+
ATP
Extracellular fluid
H+
65
Fermentation : Breakdown of organic

molecules to produce energy without oxygen.
Many organisms can only use O2 as final electron acceptor Make ATP via glycolysis only:
The problem:
Glycolysis
needs NAD (to continue) and generates
NADH NADH produces free radicals in high concentrations We need to reduce the NADH to NAD
66
The solution
Muscle cells produce lactate (lactic acid)

The The
pyruvate is converted to lactate.
electrons to reduce pyruvate to lactate are derived from oxidation of NADH which produces NAD. oxygen is restored the lactate is converted back to pyruvate for energy or may be converted to glucose by the liver.
Once
Yeast cells make ethanol
The pyruvate is broken down to CO2 and acetaldhyde.

The acetaldehyde is reduced to ethanol by oxidation of NADH to NAD Fermentation produces far less ATP (2 ATP per glucose molecule) than oxidative phosphorylation
(34-38 ATP).
2 ADP + 2 Pi
2 ATP
O
C O C O
2 ADP + 2 Pi
2 ATP
O C O C O
Glucose
Glycolysis
CH3 2 pyruvate
Glucose
Glycolysis
CH3 2 pyruvate
O
C O H C OH CH3
2 NAD+ + 2 H+
2 NADH H H C OH CH3
2 NAD+ + 2 H+
2 NADH
H C O
2 CO2
2 H1
2 H+
CH3 2 acetaldehyde
2 lactate (secreted from the cell) (a) Production of lactic acid
2 ethanol (secreted from the cell) (b) Production of ethanol

(weights): Bill Aron/Photo Edit; (wine barrels): Jeff Greenberg/The Image Works
69
END HERE
SKIP SECTION 7.3
Secondary Metabolism
Primary metabolism- essential for cell structure and function Secondary metabolism- synthesis of secondary metabolites that are not necessary for cell structure and growth Secondary metabolites unique to a species or group Roles in defense, attraction, protection, competition
71
4 categories
Phenolics
Antioxidants
with intense flavors and smells
Alkaloids
Bitter-tasting
molecules for defense
Terpenoids
Intense
smells and colors weapons

72
Polyketides
Chemical
73
74
75
76
1. Identify the 4 steps of glucose metabolism.

2. What is the purpose for changing glucose into fructose1,6 bisphosphate? 3. Where do the Phosphates come from for the above reaction?
4. The citric acid cycle is controlled by ____________.
5. The equation,
C6H12O6+ 6O2 6CO2+ 6H2O (ATP + Heat),
describes which of the following processes? A. photosynthesis B. cell respiration C. cell fermentation D. glycolysis E. anaerobic metabolism
6.What is produced from pyruvate in muscle cells under anaerobic conditions?
Which of the following processes will occur in the presence or absence of oxygen? A. glycolysis B. electron transport chain C. oxidative phosphorylation D. cellular respiration E. citric acid cycle

7 REV 1406 Lecture

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CHAPTER 7 LECTURE SLIDES

When we breath we take in the oxygen needed for cellular respiration)

Aerobic respiration uses oxygen

consumed and CO2 released

Focus on glucose but other organic molecules also used.

Outer mitochondrial membrane

2 pyruvate 2 C C C 2 NADH 2 NADH 2 pyruvate

Inner mitochondrial membrane

Breakdown of pyruvate: 2 pyruvate 2 C C C

Citric acid cycle: 2 acetyl

2 CO2 2 acetyl 4 CO2 2 CO2

Via substrate-level phosphorylation

Via substrate-level phosphorylation

Net yield in ATP of 2

occurs in the cytosol

Phase 1 Energy investment phase

The cleavage phase (steps 4-5) breaks the six carbon

Energy investment phase

Two molecules of glyceraldehyde3-phosphate

Step 6, glyceraldehyde-3-phosphate is oxidized to yield NADH. (x2)

Energy investment phase

CH2O P Pi NADH ATP ATP

Two molecules of glyceraldehyde3-phosphate

Two molecules of pyruvate

Glycolysis Net yield is 2 ATP and 2 NADH and 2 pyruvate molecules.

1. Glucose is phosphorylated by ATP.

2. Glucose-6-phosphate is rearranged into fructose-6-phosphate

3. Fructose-6-phosphate is phosphorylated to make fructose-1,6-bisphosphate (ATP is used)

4. Fructose-1,6-bisphosphate is cleaved into Dihydroxyacetone and Glyceraldehyde-3-phosphate

Dihydroxyacetone is isomerized into another glyceraldehyde-3-phosphate the result is 2 glyceraldehyde-3-phosphate

5. The Dihydroxyacetone phosphate is Isomerized into Glyceraldehyde-3-phosphate.

Citric acid cycle 2 CO2 2 CO2

+3034 ATP ATP ADP

6. Glyceraldehyde-3-phosphate is oxidized to 1,3bisphosphoglycerate with the production

The phosphate group is destabilized making it ready for exergonic reaction

Unstable phosphate bond

CHOH CH2O P Glyceraldehyde3-phosphate 2 Pi dehydrogenase

CHOH CH2O P Phosphoglycero kinase

8. The phosphate group is moved in 3-phosphoglycerate to form 2-phosphoglycerate

Unstable phosphate bond

CHOH CH2O P Glyceraldehyde3-phosphate 2 Pi dehydrogenase

Unstable phosphate bond

Unstable phosphate bond

CHOH CH2O P Glyceraldehyde3-phosphate 2 Pi dehydrogenase

CHOH Phosphoglycero CH2O kinase

Unstable phosphate bond

CHOH CH2O P Glyceraldehyde3-phosphate 2 Pi dehydrogenase

CHOH Phosphoglycero CH2O kinase

O C O C O Outer CH3 membrane channel H+/pyruvate symporter H+ O C O

Pyruvate dehydrogenase S CoA C O + CO2 + NADH CH3 Acetyl CoA

O C O C O Outer CH3 membrane channel H+/pyruvate symporter H+ O C O

Pyruvate dehydrogenase S CoA C O + CO2 + NADH CH3 Acetyl CoA

Stage 3: Citric acid cycle

2 NADH 2 NADH 6 NADH 2 FADH2

2 pyruvate 2 CO2 Breakdown of pyruvate +2 ATP

Citric acid cycle

1. An acetyl group from acetyl CoA is attached to oxaloacetate to form citrate

COO CH2 HC COO

H2O Citrate synthetase

2. Citrate is rearranged to an isomer called isocitrate

COO CH2 HC COO CH2 HO C CH2 COO COO HO CH COO COO

COO CH2 CH2

H2O Citrate synthetase